Action Points

Changes in joint damage and inflammation, detected with magnetic resonance imaging (MRI) as early as 12 weeks, predict changes in joint damage evident on subsequent x-rays in patients with rheumatoid arthritis (RA).

Note that the authors concluded that MRI can detect progression of structural damage in RA randomized controlled trials as soon as 3 months, and discriminate inhibition of progression of joint damage within this time frame in placebo-controlled trials with about 30 to 70 patients per treatment arm.

Changes in joint damage and inflammation, detected with magnetic resonance imaging (MRI) as early as 12 weeks, predict changes in joint damage evident on subsequent x-rays in patients with rheumatoid arthritis (RA), new research has found.

In the study, published in the Annals of the Rheumatic Diseases, the authors, led by Charles Peterfy, MD, PhD, founder and CEO of Spire Sciences Inc., in Boca Raton, Fla., recommend using MRI to assess inflammation and joint damage in short-duration randomized controlled trials (RCTs) in RA.

"MRI is a valid imaging method for evaluating inflammation and joint damage in rheumatoid arthritis, and it detects changes in these disease features earlier than radiography does," Peterfy told MedPage Today. "MRI should be accepted for evaluating structure-modifying treatment efficacy in phase III clinical trials."

In the interview he stressed that he was speaking only for himself and that his views are not necessarily those of the other authors of the report.

Radiography is the only imaging tool now accepted by the FDA for assessing structural damage in phase III clinical trials of RA, but as effective structure-modifying therapies become available, it has become unethical to withhold treatment from patients in placebo-controlled trials for extended periods of time, he explained.

"The most recent regulatory guidance limits this to only 12 weeks. However, longer time intervals -- i.e., 24 or more weeks -- are typically needed to discriminate a treatment effect reliably with radiography. This has created a demand for faster and more sensitive imaging tools for assessing disease progression and treatment response in RA."

Numerous studies have shown that MRI is more sensitive than x-ray in identifying joint damage and detecting synovitis and osteitis more sensitively than is possible with clinical examination alone.

A task force of the American College of Rheumatology imaging subcommittee (OMERACT) pooled data from four RCTs of patients with active RA that included serial MRIs (baseline to 12 and/or 24 weeks) and x-rays (baseline to 24 and/or 52 weeks). Data included information on 1,022 hands and wrists.

The study found that progression of MRI erosion scores at weeks 12 and 24 predicted progression of x-ray erosions at weeks 24 and 52, with areas under the curve (AUCs) of 0.64 (95% confidence interval [CI] 0.54-0.75) and 0.74 (95% CI 0.66-0.82), respectively.

In three of the trials, an analysis of the prediction of x-ray erosion progression at week 24, based on 12-week MRI progression in osteitis, showed an AUC (0.78; 95% CI 0.70-0.86), which the authors described as "near excellent."

MRI changes in synovitis at weeks 12 and 24 also predicted progression of x-ray joint damage at weeks 24 and 52 (AUCs of 0.72 and 0.65, respectively).

A limitation of the study was that some trial data sets could not be included because they did not have earlier MRI followed by later x-ray outcomes.

Another limitation was that all but one of the four data sets allowed for rescue therapy in placebo patients by 24 weeks, which confounded analyses based on x-ray data over longer time intervals.

"This limitation highlights why a method, such as MRI, that is sensitive enough to discriminate treatment effect within only 12 weeks -- that is, before rescue treatment -- is needed," the researchers wrote.

Summing up, Peterfy said that the study study adds to the evidence that MRI may fill the need for faster and more sensitive imaging tools, "given its ability to discriminate treatment response with respect to the same structural outcomes that radiography focuses on, but more quickly -- often within only 12 weeks -- and with fewer patients."

MRI is also able to show treatment effects on the upstream inflammatory drivers of structural damage in RA -- namely, synovitis and osteitis -- in even less time (as little as 2 weeks) -- based on the findings of this and other studies, he added.

The new information may also be useful in clinical practice. "Earlier, more accurate identification of patients expressing the erosive phenotype of RA based on MRI would allow earlier and more accurate assignment of treatment for these patients. Further, verifying treatment response, or lack of it, earlier and more accurately would allow more timely adjustment of therapy in treat-to-target management strategies, and presumably improve patient outcomes."

Independent grant support was provided by Bristol-Myers Squibb, Genentech/Roche, Janssen, and Pfizer; and data were provided by Amgen, Genentech/Roche, and Janssen.

Peterfy reported having other competing interests from his company, Spire Sciences, outside this study.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.